J. Org. Chem. 1989,54,5409-5411
Proximal functionalization at the lower rim of calix[4]arenes is unprecedented in the literature. Several authors3J4-lehave observed regioselective distal alkylation by using a variety of electrophiles, such as diazomethane, methyl tosylate, allyl bromide, benzyl bromide, a-bromoacetates, a-halo ketones, and chloroacetonitrile. Steric factors and stabilizing hydrogen bond effects of the de(13) 3b: 'H NMR (CDCIS,250 MHz) 6 3.28 and 4.41 (AB q, J = 13.0 Hz, ArCHzAr, 4 H), 3.37 and 4.36 (AB q, J = 13.7 Hz, ArCHzAr, 2 H), 3.48 and 4.65 (AB q, J = 12.7 Hz, ArCHzAr, 2 H), 4.88 and 5.34 (ABq, J = 13.0 Hz. 0CH.Pv. 4 HI. 6.58 (t. J = 7.5 Hz. ArH. 2 HI. 6.78 (t. J =
154.31, and 157.20. (14) Ungaro, R.; Pochini, A.; Andreetti, G. D. J. Zncl. Phenom. 1984, 2, 199. (15) Collins, E. M.; McKervey, M. A.; Harris, S.J. J. Chem. SOC., Perkin Trans. 1 1989, 372. (16) van Loon, J.-D.; Arduini, A.; Verboom, W.; Ungaro, R.; van Hummel, G. J.; Harkema, S.;Reinhoudt, D. N. Tetrahedron Lett. 1989, 30, 2681.
5409
protonated monoalkylated species have been proposed to play an important role in determining the regioisomeric outcome.16 In our case, the reversed regioselectivity may be ascribed to the tendency of the pyridine pendant group in the monoalkylated intermediate to establish favorable hydrogen bonding with the nearest hydroxy group, which results in a remarkable enhancement of its acidity and reactivity. The above effects are also believe to exert an important role in keeping and stabilizing calix[4]arenes 3-6 in the cone conformation. The synthetic approach leading to proximal disubstituted calix[4]arenes in the cone conformation opens up new perspectives for the construction of calix[l]arenes with mixed ligating groups, for the synthesis of chiral trisubstituted calix[4]arenes, and for the selective proximal difunctionalization at the "upper rim".
Acknowledgment. We wish to thank the Italian Ministry of Education for partial financial support of this work and Professor Rocco Ungaro for helpful discussions. Supplementary Material Available: Experimental procedures and characterizationdata for 2a-c, 4,5a, and 6a,b (4 pages). Ordering information is given on any current masthead page.
Dramatic Changes in Diastereoselectivity with the Quantity of Titanium Tetrachloride Used in Lewis Acid Mediated Reactions of Allylsilane with a-Amino Aldehydes' Syun-ichi Kiyooka,* Masahito Nakano, Fuminori Shiota, and Ryoji Fujiyama Department of Chemistry, Kochi University, Akebono-cho, Kochi 780, J a p a n
Received J u n e 8, 1989
Summary: Dramatic changes in diastereoselectivity, depending upon the quantity of titanium tetrachloride used in the Lewis acid mediated reactions of allylsilane with chiral a-N-(carbobenzy1oxy)aminoaldehydes (1,3, and 5), have been observed. These results are discussed, and the possibility that a 2:l complex of aldehyde and TiCl, is being generated and its role are proposed. Sir: Over the past 10 years, the Lewis acid mediated reactions of silyl nucleophiles with aldehydes and several other electrophiles have attracted the interest of synthetic organic chemists, especially from the standpoint of stereoselectivity.2 While the development of this methodology has been impressive, a variety of reaction conditions have been adopted in order to make the reaction more selective. I t has been become customary for synthetic organic chemists to weigh a slightly excessive amount of TiC1, and transfer it into the reaction flask via a syringe in lab-scale (millimole) experiments, but the molar ratios of TiC1, to aldehyde are not necessarily accurate in this procedure. Furthermore, it has not been possible to determine the minimum quantity of TiC14required in order (1)Presented in part at the 58th Annual Meeting of the Chemical Society of Japan, Kyoto, April 1-4, 1989 (Abstracts of Papers, p 1624). (2) Hoaomi, A,; Sakurai, H. Tetrahedron Lett. 1976,1295. Hoffmann, R. W. Angew. Chem., Int. Ed. Engl. 1982,21,555. Weidmann, B.; Seebach, D. Zbid. 1983,22,31. Reetz, M. T. Ibid. 1984,23,556. Heathcock, Blumenkopf, T. A. J. Org. Chem. 1984, 49, 4214. C. H.; Kiyooka, 5.-I.; Heathcock, C. H.; Davidsen, S.K.; Hug, K. T.; Flippin, L. A. Zbid. 1986 51,3027. Keck, G. E.; Castellino, S.;Wiley, M. R. Ibid. 1986,51,5478. Reetz, M. T. Organotitanium Reagents in Organic Synthesis; Spring er-Verlag: Berlin, 1986. Yamamoto, Y. Acc. Chem. Res. 1987, 20, 243. Reetz, M. T.; Jung A.; Bolm, C. Tetrahedron 1988,44,3889. Fujisawa, T.; Ukaji, Y. Yuki Gosei Kagaku Kyokaishi 1989,47, 186.
0022-326318911954-5409$01.50/0
a,b +
hPO , ,N H 5
a
anti-6
syn-6
(a) TiC4-CH2Cl2,allylsilane, -78 OC; (b) H 80'.
to provide satisfactory yields in the so-called stoichiometric TiC1,-mediated reactions of allylsilane with aldehydes3 We disclose herein that the quantity of Lewis acid (Tic,) added significantly affects the stereoselectivity in the Lewis acid mediated reactions4with three structurally (3) Kiyooka, S.;Nakano, M., unpublished results. The TiCl,-mediated reaction of allylsilane with 2-phenylpropanalgave the product in ca.80% yield by using 0.5 molar equiv of T i c 4 , but the reaction with less than 0.4 molar equiv of TiC14 failed.
0 1989 American Chemical Society
5410
J. Org. Chem., Vol. 54, No. 23, 1989
Communications
Table I. Diastereoseleotivity as a Function of the Quantity of TiCl, entrv 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
aldehvde 1 1 1 1 1 1 1 1 3 3 3
3 3 3 5 5 5 5 5 5 5
molar equiv of TiC1, 0.4 0.5 0.7 0.8 1.0 1.2 1.5 2.0 0.5 0.6 0.7 0.8 1.0 1.5 0.5 0.6 0.7 0.8 1.0 1.2 1.5
ratio" svn:anti 7: 1
81 1:2 1:9 1:20 1:3
1:l 1:l 28:l 26:l 6.5:1
1:l 1:l 1:l 1:l 1.51 3: 1 12:l 141 15:l 13:l
yield,* '3 17c 47 56 72 84 80 78 69 63 70 73 80 89 91 15d 46 62 78 82 79 65
"Determined b 13C NMR spectroscopy, with averages of at least three runs. {Isolated yield after chromatography. CThisreduction in yield might arise from the stoichiometry of the reaction (ref 3). addition, an unknown ketonic compound was obtained in ca. 35% yield; the structural determination is underway.
'\
J"x
07 1
0
040.5
w
trans
7.25
3.96
7.20
4.17
1 0
2 .o
1.5
Molar e q u i v of T i C 1 4
:l!
20
B
L
Table 11. J Values between 4-H and 5-Hin 4,s-Disubstituted Oxazolidin-2-ones cis
1.2
0 8
b Molar e q u i v of T i c 1 4
0
K0
C
L
L I 5
Molar e q u i v of T i c 1 4
0
distinct aldehydes6 derived from a-amino acids. The results are briefly summarized in Table I; the syn/anti stereochemistry of products was assigned on the basis of that of the corresponding 4,5-disubstituted oxazolidin-2ones, as shown in Table II.6 (4) (a) Dependence of diastereoselectivity of Lewis acid catalyzed Diels-Alder reaction (TiCIJ: Poll, T.; Sobczak, A.; Hartmann, H.; Helmchen, G. Tetrahedron Lett. 1985, 26, 3095. (b) Intramolecular allylation (SnCl,): Denmark, S.E.; Henke, B. R.; Weber, E. J. Am. Chem. SOC.1987, 109, 2512. (5) The Cbz group was used instead of the Boc group because of its stability toward acidic conditions. N-Cbz-L-serinalacetonide 1: [ a ] " ~ -69' (c = 1.00, CHC18),waa prepared by DIBAL reduction (-78 "C) of the acetonide obtained from N-Cbz-L-serine methyl ester; the optical purity was not determined. The aldehydes of 3 and 5 were obtained in a similar procedure: N-Cbz-prolinal, [a]*lD -70' (c = 1.08, CHCl,); NCbz-valinal, [aIno +63O (c = 1.09, CH,Cl,). (6) A mixture of syn-2 and anti-2 could not be separated by chromatography, but protection of their primary hydroxy groups with TBDSCl permitted separation of the isomers; mixtures of syn-4lanti-4 and syn5/anti-5 were separable. These isomers were converted to the corresponding 4,5-disubstituted oxazolidin-2-onesunder the usual basic conditions. The coupling constants between 4-H and 5-H of the derivatives are known to be cis > trans: Fujikawa, S.;Inui, T.; Shiba, T. Bull. Chem. SOC.Jpn. 1973,43, 3308. Garigipati, R. S.;Freyer, A. J.; Whittle, R. R.; Weireb, S. M. J.Am. Chem. SOC. 1984,106,7861. Kano, S.;Yokomatsu, T.; Iwasawa, H.; Shibuya, S. Tetrahedron Lett. 1987,28, 6331; Chem. Lett. 1987, 1531.
Figure 1. Observed diastereoselectivity as a function of the quantity of titanium tetrachloride used in the reactions of NCbz-serinalacetonide 1 (A), N-Cbz-serinal3(B), and N-Cbz-valinal 5 (C) with allylsilane.
A high anti stereoselectivity (20:l) was observed in the reaction of allylsilane with N-Cbz-L-serinal acetonide l.'t8 The magnitude of this selectivity, however, was not always constant. Thus, a detailed study of the reaction conditions was undertaken which led to two improvements. First, in order to measure conveniently and accurately the required quantity of Tic4,a 1M TiC14solution in dichloromethane was prepared; an aliquot from the solution was then transferred via syringe into the reaction flask. Second, to the precooled TiC14solution (-78 OC) was added a solution of the aldehyde in CH2C1, slowly over the course of 30 min; the resulting solution was then stirred for more than 1h (7) Syn selectivity on N-Boc-serinal acetonide. ZnC1,: Garner, P. Tetrahedron Lett. 1984,25,5855. A1 reagent: Newman, H. Zbid. 1971, 4571. Mg-CuI reagent: Herold, P. Helu. Chim. Acta 1988, 71, 354. (8) Anti selectivity on N-Boc-serinalacetonide. (a) Lithium reagents: Gamer, P.; Park, J. M.; Malecki, E. J. Org. Chem. 1988,53,4395. Herold, P. Helu. Chim. Acta 1988, 71,354. Nimkar, S.;Menaldino, D.; Merrill, A. H.; Liotta, D. Tetrahedron Lett. 1988,29, 3037. (b) Si-F reagent: Dondoni, A.; Fantin, G.; Fogagnolo, M.; Medici, A. Tetrahedron 1987,43, 3533.
J. Org. Chem. 1989,54, 5411-5413 CI C I CI CI,\/ TI'
07P h
Ph
A
B
Figure 2.
in order to allow time for the coordinative interactions between the aldehyde and TiC1, to be completely established at this low temperature. After adding allylsilane over the course of 30 min and stirring for 20 min, the reaction was then quenched with water.g From the above experiments, it was shown that the quantitiy of T i c 4 added is clearly an important factor in controlling the reaction course. The reaction selectivity versus the quantity of TiC14 added produced a unique curve, as shown in Figure 1A. Undoubtedly, maximum anti selectivity was observed with values near 1.0 equiv. of TiCl,, but the range of effective concentrations of TiC1, over which the anti isomer dominated was very limited. The anti selectivity decreased as the quantity of TiC14was decreased from 1.0 molar equiv, and the syn isomer was, surprisingly, ultimately favored over the anti by a ratio of 8:l with 0.5 equiv of TiC1,. On the other hand, the anti selectivity rapidly decreased as the quantity of TiC14was increased over 1.0 equiv. We interpret this trend in terms of two differently derived species (aldehyde-TiCl,, 1:l and 2:l complexes), which could proceed to the respective transition states. The existence of substrateLewis acid 2:l complexes has been previously reportedlo in solid and/or solution states. Thus, the selectivity found with 0.5 equiv of TiCl, could be described as arising from reaction via the 2:l complex. On the other hand, the anti selectivity observed with 1.0 equiv is consistent with @-chelation,a characteristic of aldehydes with @-alkoxygroups; in such cases, @-chelation
5411
is more effective than a-chelation (Figure 2A). The disturbance of @-chelation,with excess TiC14 over 1.0 equiv, resulted in lower anti selectivity. In the case of N-Cbz-prolinal 3, it is extremely interesting to note that high syn selectivity" (281) was obtained in the reaction with 0.5 equiv of TiC14,but not with 1.0 equiv, as shown in Figure 1B. This selectivity apparently arises from a transition state via the aldehyde-Tic4 2:l complex and is consistent with the result with serinal 1. The complete lack of selectivity with 1.0 equiv is undoubtedly attributable to the difficulty in achieving achelation, which must intervene between the aldehyde carbonyl and N-Cbz groups. In contrast, the reaction of acyclic N-Cbz-valinal5 using 1.0 equiv of TiCl, resulted in high syn selectivity, which tends to substantiate the validity of an ordinary a-chelation mechanism, via a 1:l complex, as shown in Figure 2B. The a-chelation in such an acyclic system is stable enough to withstand the presence of excess TiCl,, as shown in Figure 1C. From this point of view, the absence of achelation in serinal and prolinal systems may be traceable to a common structure which contains the a-cyclic moiety. A similar syn selectivity, in a 5:l ratio, was observed in the case of N-Cbz-phenylalaninal, as expected. The diastereofacial selectivity is obviously achieved via conformations demanding entirely different steric factors, in the case where a-chelation is hindered by the inherent structural characteristics of the aldehydes (1 and 3) in the Lewis acid mediated reactions. We accordingly invoke the role of an aldehydeTiC14 21 complex, in order to explain the high syn stereoselectivityunexpectedly observed at 0.5 molar equiv of TiC14. It could be envisioned that the diastereoface may be amphiphilically12 distinguished by the second aldehyde coordinated to the TiC14,as shown in Figure 2C. Further studies on diastereoselectivity as it pertains to the quantity of Lewis acid used, on representative acyclic aldehydes, are in progress and will be reported in due course. Acknowledgment. This research was supported by a Grant-in-Aid (No. 1540430) from the Ministry of Education, Science, and Culture of Japan.
~~
(9) After acidic workup, the crude allylated materials consisted of
deprotected product and five- and six-membered acetonidea; treatment with 10% HCl-THF gave a mixture of syn-2 and anti-2. (IO) TiCl4
